Cor Pulmonale in Cystic Fibrosis

ABSTRACT

Cystic fibrosis is a common autosomal recessive disorder that is associated with a defective chloride transport channel in epithelial cells. The discovery of the cystic fibrosis gene in 1989 has led to a better understanding of the pathophysiology of the disease and the development of more effective therapeutic interventions. Chronic recurrent lung infections, pancreatic exocrine insufficiency, and elevated sweat chloride levels are hallmarks of the disease. Survival of patients with cystic fibrosis is steadily improving and most patients survive into adulthood. As lung disease progresses, secondary pulmonary hypertension and cor pulmonale are likely to develop. Pulmonary hypertension is correlated with the degree of hypoxemia and may be associated with increased mortality. The goal of therapy of cor pulmonale in cystic fibrosis is to correct hypoxemia and lower the elevated pulmonary artery pressures. This is best achieved by supplemental oxygen and aggressive treatment of the pulmonary disease with antibiotics and airway clearance techniques. It is also important to assess oxygenation during sleep and exercise. Bilateral lung transplantation is a treatment option for patients with end-stage lung disease, even in the presence of cor pulmonale.

KEYWORDS

Cystic fibrosis - pulmonary hypertension - cor pulmonale - oxygen therapy

REFERENCES

• 1 Kosork M R, Wei W H, Farrell P M. The incidence of cystic fibrosis.  Stat Med . 1996;  15 449-462
• 2 Cystic Fibrosis Foundation. Patient Registry 2000 Annual Report. Bethesda, MD: Cystic Fibrosis Foundation; 2001
• 3 Yankaskas J R, Knowles M R. Cystic Fibrosis in Adults. Philadelphia: Lippincott-Raven 1999: 45-67
• 4 Cystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic Fibrosis Washington, DC: Cystic Fibrosis Foundation; 1997
• 5 Riordan J R, Rommens J M, Kerem B. et al . Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.  Science . 1989;  245 1066-1073
• 6 Kerem E, Corey M, Kerem B S. et al . The relationship between genotype and phenotype in cystic fibrosis: analysis of the most common mutation (ΔF508).  N Engl J Med . 1990;  323 1517-1522
• 7 Stern R C. The diagnosis of cystic fibrosis.  N Engl J Med . 1997;  336 487-491
• 8 Welsh M J, Anderson M P, Rich D P. et al .Cystic fibrosis, CFTR, and abnormal electrolyte transport. In: Davis PB, ed. Cystic Fibrosis New York: Marcel Dekker 1993: 29-52
• 9 Cutting G R. Genotype defect: its effect on cellular function and phenotypic expression.  Sem Respir Crit Care Med . 1994;  15 356
• 10 Seeger W, Suttorp N. Role of membrane lipids in the pulmonary vascular abnormalities caused by bacterial toxins.  Am Rev Respir Dis . 1987;  136 462-466
• 11 Stern R. Inpatient treatment of cystic fibrosis pulmonary disease. In: Orenstein DM, Stern RC, eds. Treatment of the Hospitalized Cystic Fibrosis Patient New York: Marcell Dekker 1998: 79-133
• 12 Ramsey B W. Management of pulmonary disease in patients with cystic fibrosis.  N Engl J Med . 1996;  335 179-188
• 13 Royce S W. Cor pulmonale in infancy and early childhood: report on 34 patients, with special reference to the occurrence of pulmonary heart disease in cystic fibrosis of the pancreas.  Pediatrics . 1951;  8 255-274
• 14 Stern R C, Borkat G, Hirschfeld S S. et al . Heart failure in cystic fibrosis: treatment and prognosis of cor pulmonale with failure of the right side of the heart.  Am J Dis Child . 1980;  134 267-272
• 15 Levesque P C, Padraig J H, Hume J R, Kenyon J L, Horowitz B. Expression of cystic fibrosis transmembrane regulator Cl-channels in heart.  Circ Res . 1992;  711 1002-1007
• 16 Hart P, Warth J D, Leresque P C. et al . Cystic fibrosis gene encodes a cAMP-dependent chloride channel in heart.  Proceedings of the National Academy of Sciences of the United States of America . 1996;  93 6343-6348
• 17 Goldring R M, Fishman A P, Turino G M, Cohen H I, Denning C R, Andersen D H. Pulmonary hypertension and cor pulmonale in cystic fibrosis of the pancreas.  J Pediatrics . 1964;  65 501-524
• 18 Symchych P S. Pulmonary hypertension in cystic fibrosis.  Arch Pathol . 1971;  91 409-414
• 19 Fraser K L, Tullis D E, Sasson Z, Hyland R H, Thornley K S, Hanly P J. Pulmonary hypertension and cardiac function in adult cystic fibrosis: role of hypoxemia.  Chest . 1999;  115 1321-1328
• 20 Viles P J, Shepherd J T. Relationship between pH, pO₂ and pCO₂ on the pulmonary vascular bed of the cat.  Am J Physiol . 1968;  215 1170-1176
• 21 Enson Y, Giuntini C, Lewis M L. et al . The influence of hydrogen ion concentration and hypoxia on the pulmonary circulation.  J Clin Invest . 1964;  43 1146
• 22 Jessup M, Sutton S G, Weber K. et al . The effect of chronic pulmonary hypertension on left ventricular size, function, and interventricular septal motion.  Am Heart J . 1987;  113 1114-1122
• 23 Jacobstein M D, Hirschfeld S S, Winnie G, Doershuk C, Liebman J. Ventricular interdependence in severe cystic fibrosis.  Chest . 1981;  80 399-404
• 24 Vizza C D, Lynch J P, Ochoa L L, Richardson G, Trulock E P. Right and left ventricular dysfunction in patients with severe pulmonary disease.  Chest . 1998;  113 576-583
• 25 Hortop J, Desmond K J, Coates A L. The mechanical effects of expiratory airflow limitation on cardiac performance in cystic fibrosis.  Am Rev Respir Dis . 1988;  137 132-137
• 26 Moss A J. The cardiovascular system in cystic fibrosis.  Pediatrics . 1982;  70 728-741
• 27 Fowler R S, Rappaport H, Cunningham K, Crozier D N, Levison H, Rowe R D. Cor pulmonale in cystic fibrosis.  J Electrocardiology . 1981;  14 319-324
• 28 Gewitz M, Eshaghpour E, Holsclaw D S, et.al. Echocardiography in cystic fibrosis.  Am J Dis Child . 1977;  131 275-280
• 29 Ionescu A A, Ionescu A, Payne N, Obieta-Fresnedo I, Fraser A G, Shale D J. Subclinical right ventricular dysfunction in cystic fibrosis.  Am J Respir Crit Care Med . 2001;  163 1212-1218
• 30 Rosenthal A, Tucker C R, Williams R G, Khaw K T, Strieder D, Schwachman H. Echocardiographic assessment of cor pulmonale in cystic fibrosis.  Pediatr Clin North Am . 1976;  23 327-344
• 31 Ryssing E. Assessment of cor pulmonale in cystic fibrosis by echocardiography.  Acta Pediatr Scand . 1977;  66 753-756
• 32 Panidis I P, Ren J F, Holsclaw D S, Kotler M N, Mintz G S, Ross J. Cardiac function in patients with cystic fibrosis: evaluation by two-dimensional and Doppler echocardiography.  J Am Coll Cardiol . 1985;  6 701-706
• 33 Piepsz A, Ham H R, Millet E, Dab I. Determination of right ventricular ejection fraction in children with cystic fibrosis.  Pediatr Pulmonol . 1987;  3 24-28
• 34 Florea V G, Florea N D, Sharma R. et al . Right ventricular dysfunction in adult severe cystic fibrosis.  Chest . 2000;  118 1063-1068
• 35 Ramsey B W, Pepe M S, Quan J N. et al . Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.  N Engl J Med . 1999;  340 23-30
• 36 Fuchs J F, Borowitz D S, Christiansen D H. et al . Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis.  N Engl J Med . 1994;  331 637-642
• 37 Konstan M W, Byard P J, Hoppel C L. et al . Effect of high-dose ibuprofen in patients with cystic fibrosis.  N Engl J Med . 1995;  332 848-854
• 38 Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.  Ann Intern Med . 1980;  93 391-398
• 39 Bradley T D, Rutherford R, Gorssman R F. et al . Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome.  Am Rev Respir Dis . 1985;  131 835-839
• 40 Stokes D C, McBride J T, Wall M A, Erba G, Strieder D J. Sleep hypoxemia in young adults with cystic fibrosis.  Am J Dis Child . 1980;  134 741-743
• 41 Coffey M J, FitzGerald M X, McNicholas W T. Comparison of oxygen desaturation during sleep and exercise in patients with cystic fibrosis.  Chest . 1991;  100 659-662
• 42 Tepper R S, Skatrud J B, Dempsey J A. Ventilation and oxygenation changes during sleep in cystic fibrosis.  Chest . 1983;  84 388-393
• 43 Becker H F, Piper A J, Flynn W E. et al . Breathing during sleep in patients with nocturnal desaturation.  Am J Respir Crit Care Med . 1999;  159 112-118
• 44 Frangolis D D, Despina D, Wilcox P G. Predictability of oxygen desaturation during sleep in patients with cystic fibrosis: clinical, spirometric, and exercise parameters.  Chest . 2001;  119 434-441
• 45 Villa M P, Pagani J, Lucidi V, Plamides S, Ronchetti R. Nocturnal oximetry in infants with cystic fibrosis.  Arch Dis Child . 2001;  84 50-54
• 46 Nixon P A, Orenstein D M, Curtis S E, Ross E A. Oxygen supplementation during exercise in cystic fibrosis.  Am Rev Respir Dis . 1990;  142 807-811
• 47 Versteegh F GA, Borgarrd J M, Raatgever J W, Stam H, Neijens J F, Kerrebijn K F. Relationship between airway obstruction, desaturation during exercise and nocturnal hypoxaemia in cystic fibrosis patients.  Eur Respir J . 1990;  3 68-73
• 48 Nixon P, Orenstein D, Kelsey S, Doershuk C. The prognostic value of exercise testing in patients with cystic fibrosis.  N Engl J Med . 1992;  327 1785-1788
• 49 Zinman R, Corey M, Coates A L. et al . Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients.  J Ped . 1989;  114 368-377
• 50 Dinwiddie R, Madge S, Prasad S A, Balfour-Lynn I M. Oxygen therapy for cystic fibrosis.  J R Soc Med . 1999;  92 (suppl 37) S19-S22
• 51 Geggel R L, Dozor A J, Flyler D C, Reid L M. Effect of vasodilators at rest and during exercise in young adults with cystic fibrosis and chronic cor pulmonale.  Am Rev Respir Dis . 1985;  131 531-536
• 52 Michael J R, Kennedy T P, Fitzpatrick S, Rosenstein B J. Nifedipine inhibits hypoxic pulmonary vasoconstriction during rest and exercise in patients with cystic fibrosis and cor pulmonale.  Am Rev Respir Dis . 1984;  130 516-519
• 53 Yankaskas J R, Mallory G B. Lung transplantation in cystic fibrosis: consensus conference statement.  Chest . 1998;  113 217-226
• 54 Yacoub M H, Banner N R, Khaghani A. et al . Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation.  J Heart Transplant . 1990;  9 459